Baculovirus is an insect specific virus; however, it can serve as an efficient vector for gene expressions in both insect and mammalian cells. Among all the baculoviruses, Autographa californica multicapsid nuclear polyhedrosis virus (AcMNPV) is the best studied. AcMNPV and Spodoptera frugiperda cells together constitute a widely used system for the production of many heterologous proteins, owing to the ease of producing large scale cultures of S. frugiperda cells. Bombyx mori NPV (BmNPV) is another widely used baculovirus gene expression system and can be used to express heterologous proteins in B. mori (silkworm) larvae with ease. Both baculoviruses have been shown capable of entering a variety of vertebrate cells, adding versatility to the baculovirus expression system. AcMNPV infects various insect species and replicates in some lepidopteran cell lines. However, this virus does not replicate or form polyhedra in B. mori cells and vertebrate cells.
MicroRNAs (miRNAs) are small RNA molecules (22 nucleotides) found in eukaryotic cells that regulate gene expression by interference during translation and/or post-transcription. Drosha is part of a multi-protein complex, the microprocessor, which mediates the nuclear processing of primary miRNAs into stem-loop precursors of approximately 60 to 70 nucleotides (pre-miRNAs). See, e.g., Lee et al., Nature, 525: 415-419 (2003). Pre-miRNAs are subsequently exported into cytomplasm via Exportin 5. In the cytoplasm, the pre-miRNAs are cleaved by Dicer into mature 22 nucleotide miRNAs. The mature miRNA is incorporate as a single stranded RNA into a ribonucleoprotein complex, known as the RNA-induced silencing complex. This complex directs the miRNA to the target mRNA, which leads either to translational repression or degradation of the target mRNA. See, e.g., Bartel, Cell, 116: 281-297 (2004); and Bartel and Chen, Nature Reviews Genetics, 5: 396-400 (2004).
Antiviral innate immunity system is the first line of host cell defense that can recognize and block viral infection. The innate immune system recognizes microorganisms and viruses via a number of pattern-recognition receptors (PRRs) including Toll-like receptors, RIG-I like receptors, NOD-like receptors, and cytosolic DNA sensing receptors, which can recognize different virus compounds known as pathogen-associated molecular patterns (PAMPs). After recognition, these PRRs can activate different signaling pathways and induce immune responses and produce interferon and cytokines to block viral gene expression or virus replication. See, e.g., Akiral et al., Cell, 124:783-801 (2006).